This COBRE Phase III application is aimed at sustaining the research infrastructure built during the first ten years of NIGMS funding. Our COBRE ?South Carolina Bioengineering Center for Regeneration and Formation of Tissues? has become a nationally recognized, collaborative center with unique strengths in bioengineering approaches to regenerative medicine. Three underlying themes define the Center's research: advance biomaterial design and application; in situ tissue repair with targeted therapies; and applying the principles of normal developmental biology to regenerative medicine or stem cell based tissue engineering. SC BioCRAFT accomplishments towards these three translational goals include the recruitment of 10 new faculty, mentoring and training of 23 COBRE target faculty, and the development of two research core facilities. Programmatic outcomes include 26 independent NIH research awards, 62 research awards from other agencies to target faculty, and >550 peer reviewed publications. South Carolina Centers of Economic Excellence: SmartState awarded three endowed chairs in Regenerative Medicine and Advanced Tissue Biofabrication in partnerships with Clemson and the University of South Carolina. SC BioCRAFT participated in the successful renewal of a statewide INBRE award with a focus on bioengineering/regenerative medicine. For this P30 application, the plan transitioning to independence of NIH/NIGMS support during the next five years is to enhance and upgrade our core technologies, to increase their competitiveness, to attract greater usage (and cost recovery), and to promote new research collaborations with our Center that can lead to submission of competitive research applications and broaden our statewide outreach, especially to other IDeA centers. A seven step, five-year strategic plan including implementing fee structures, pilot projects/voucher program, outreach activities and programmatic development is proposed to sustain the SC BioCRAFT/COBRE center and its scientific cores (Biomaterials Engineering and Testing and Translational Research Imaging). The founding director of Clemson's SC BioCRAFT COBRE will lead the Administrative Core and will be assisted by two outstanding scientists from Medical University of South Carolina who have themselves directed COBREs. Together, these three leaders will act as the main operational arm of the Center. An External Advisory Committee will provide ongoing assessment and evaluation of the Center's progress. Institutional commitments from the Vice President for Research, ~2 million dollars, will help ensure programmatic growth development and long- term sustainability of the Center.